Summary: For decades, neuroscientists believed that fine, voluntary hand movements in humans were almost exclusively the responsibility of the cerebral cortex—the brain’s advanced “command center.” However, a groundbreaking study has identified an evolutionarily older pathway in the brainstem and spinal cord that is essential for manual dexterity.
By comparing fMRI scans of mice and humans, researchers discovered a shared, multi-stage relay system that integrates cortical signals with the medulla and specific cervical segments of the spinal cord (C3–C4). This discovery reveals a “backup system” for movement that could become a primary target for restoring hand function in stroke survivors.
Key Facts
- The New Map: Voluntary hand movement doesn’t just go from the brain to the muscle; it passes through relay centers in the medulla (lowest brainstem) and the C3–C4 propriospinal system in the neck.
- Evolutionary Conservation: Despite the complexity of human hands, the underlying circuitry is striking similar to that of mice, suggesting this is a fundamental mammalian architecture for limb control.
- Dual Control: While the cortex initiates movement, these brainstem structures play a vital role in coordinating and manipulating objects.
- Stroke Potential: Identifying this “overlooked” pathway offers a new target for neuromodulation therapies, potentially helping patients bypass damaged cortical areas to regain use of their hands.
Source: UCR
Researchers have identified a network of connections linking the brainstem and spinal cord that helps control hand and arm movements, revealing an unexpected layer of the nervous system enabling people to grasp, hold, and manipulate objects.
The UC Riverside-led research, published in the Proceedings of the National Academy of Sciences, shows that signals controlling voluntary hand movements travel not only directly from the brain to the spinal cord, but also through relay centers in the brainstem and topmost segment of the spinal cord.
By mapping this pathway, researchers say the work could help guide new therapies aimed at restoring hand and arm function after stroke or other neurological injuries.
The brainstem is a narrow stalk of tissue at the base of the brain that connects the brain to the spinal cord and regulates many fundamental functions such as breathing, posture, and balance. The outer cortex, the brain’s large, wrinkled outer layer, is traditionally considered the command center for voluntary movement and conscious thought.
“For a long time, we thought fine hand movements in humans were controlled almost entirely by the cortex,” said Shahab Vahdat, an assistant professor of bioengineering at UCR, who led the study. “What we are observing is that evolutionarily older brainstem structures also play an important role.”
The researchers observed activity in two regions of the medulla, the lowest portion of the brainstem that sits just above the spinal cord and helps regulate essential processes such as breathing and heart rate. The medulla also acts as a major crossroads for signals traveling between the brain and body.
To investigate how these systems interact, the team used functional magnetic resonance imaging, or fMRI, to examine brain activity during controlled hand movements in both mice and humans.
In mice, animals were trained to press a small lever with their forepaw while researchers recorded activity in the brain and brainstem. Human volunteers performed a similar task in the scanner, squeezing a device with varying levels of force using their fingers.
“We wanted to see whether the same underlying network that controls forelimb movement in rodents might also exist in humans. It wasn’t a given, since humans have more advanced motor control,” Vahdat said. “Despite the differences between our brains, we found striking similarities in how these regions communicate.”
The scans revealed two regions of the medulla that were consistently active during the tasks and strongly connected with sensorimotor areas of the brain. The same regions appeared in both species, suggesting the underlying circuitry is conserved across mammals.
The study also shows for the first time, by measuring brain activity in humans, that two segments of the spinal cord in the neck, cervical levels C3 and C4, help control the hand by acting as a relay between the brainstem and the lower spinal cord that directly activates hand muscles.
Together, the findings suggest that voluntary hand movement relies on a multi-stage pathway in which signals from the cortex are integrated with brainstem and spinal networks before reaching the muscles.
The work may also have implications for stroke rehabilitation. Damage to cortical motor regions often leaves patients with lasting difficulty using their hands, and identifying additional movement pathways could provide new targets for neuromodulation therapies designed to stimulate surviving circuits.
“These pathways give us additional targets to explore,” Vahdat said. “If we can engage them after a stroke, they may help compensate and restore function in the hands and arms.”
Key Questions Answered:
A: That’s what we were taught for a long time! But it turns out your hands have an “assistant director” in the brainstem. While the cortex handles the high-level plan, a pathway through the medulla and the upper part of your neck (C3-C4) helps execute the fine details. It’s a multi-stage process, not a direct line.
A: It shows that the “machinery” for grasping and holding is ancient. Even though humans have developed much more advanced manual skills (like playing the piano or surgery), we are still using the same evolutionary foundations as other mammals. This is great for research because it means we can study these circuits in detail to find new medical treatments.
A: When a stroke damages the motor cortex, the main “highway” to the hand is cut off. But since we now know there are these other “relay stations” in the brainstem and neck, scientists can try to stimulate those areas instead. If we can teach the brain to use these alternative pathways, we might be able to restore movement that was thought to be lost forever.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this motor control and neuroscience research news
Author: Jules Bernstein
Source: UCR
Contact: Jules Bernstein – UCR
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Medullary and C3–C4 propriospinal pathways underlying mammalian forelimb movement control” by Vishwas Jindal, Matteo M. Grudny, Daniel W. Wesson, David E. Vaillancourt, and Shahabeddin Vahdat. PNAS
DOI:10.1073/pnas.2518217123
Abstract
Medullary and C3–C4 propriospinal pathways underlying mammalian forelimb movement control
Classic models associate goal-directed upper limb movements with cortical motor areas and balance control with the brainstem.
However, recent rodent studies suggest that medullary regions and local spinal circuits also contribute to forelimb execution, leaving it uncertain if these findings apply to humans.
Critically, the dynamic interactions among medullary motor regions, intersegmental spinal networks, and cortical sensorimotor areas during hand movement control remain poorly understood.
Here, through functional MRI (fMRI) studies in humans and mice during forelimb movement tasks, we reveal topographically organized corticomedullary networks, comprising the lateral rostral medulla (Lat-RM) and caudal medulla (CauM), that regulate forelimb movement.
In mice, the corticomedullary coupling in both CauM and Lat-RM increased systematically along a ventro-medio-dorsal gradient, with the strongest links to primary motor and premotor cortices.
In humans, higher‐order sensorimotor regions drove the strongest connectivity with CauM and Lat-RM, while the more medially located medial rostral medulla remained weakly engaged.
Furthermore, simultaneous brain-spinal fMRI revealed distinct functional territories within the human C3–C4 cervical spinal cord, with ventral regions exhibiting strong connectivity to the medulla and dorsal regions to lower cervical segments.
Together, our findings identify a conserved corticomedullary network underlying forelimb movement control across species, while also uncovering variation in cortical involvement.
They indicate the presence of an indirect pathway involving both the reticulospinal pathway and the C3–C4 propriospinal system, which contributes to fine hand motor control in the mammalian brain.
